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Effects of methyl-beta-cyclodextrin on T lymphocytes lipid rafts with aging.

Abstract：

:Aging is associated with a decline in immune functions. Among them, T-cell activation is altered at several points of the signaling cascade following TCR engagement. Recent findings suggest that lipid rafts act as a platform in the initiation of T-cell activation. We have previously demonstrated that cholesterol content in T-cells increased with aging, especially in lipid rafts. Cholesterol, which is a major component of lipid rafts, serves to stabilize their structure. We hypothesized that restoring T-cell cholesterol content and membrane fluidity would restore, at least in part, T-cell function via lipid rafts. We measured the lipid rafts coalescence, the p56(Lck) and linker of activated T-cell (LAT) signaling molecules recruitment and activation, the cholesterol content and fluidity in T-cell membrane after different methyl-beta-cyclodextrin (MBCD) treatments. Our results show that high concentration of MBCD (10 mM) completely disorganized the lipid rafts in T-cell membranes of young and elderly donors, however, T-cells from elderly donors were less sensitive than T-cells of young donors to low concentration of MBCD (0.5 mM). p56(Lck) and LAT recruitment and activation were affected in T-cells of both aged groups. MBCD treatment did not affect the cholesterol content and fluidity of T-cell membranes of young donors, while the cholesterol content was decreased and fluidity increased in lipid rafts of elderly donors. These results suggested that cholesterol extraction by MBCD increased the fluidity and disrupted lipid rafts organization. The increase in cholesterol content in lipid rafts with aging and its decrease by biochemical extraction were able to affect early signaling molecules activation. Restoring cholesterol content and fluidity may have beneficial effects, however, MBCD disorganized the membrane and this might not completely restore the T-cell activation via lipid rafts with aging. Altogether these results suggest that defects in cholesterol cellular homeostasis may be part of T-cell immunosenescence via lipid rafts dysfunction.

journal_name

Exp Gerontol

journal_title

Experimental gerontology

authors

Larbi A,Douziech N,Khalil A,Dupuis G,Gheraïri S,Guérard KP,Fülöp T Jr

doi

10.1016/j.exger.2003.10.031

keywords:

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

551-8

issue

eissn

0531-5565

issn

1873-6815

pii

S0531556504000336

journal_volume

pub_type

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Effects of methyl-beta-cyclodextrin on T lymphocytes lipid rafts with aging.